Tolmetin Sodium loaded thermosensitive mucoadhesive liquid suppositories for rectal delivery; strategy to overcome oral delivery drawbacks

AbstractTolmetin sodium (TS) is a non-steroidal anti-inflammatory drug (NSAID) indicated for treatment of musculoskeletal issues. As other NSAID, TS displays a marked side effects on the gastro-intestinal (GI) tract after oral administration. Tradational solid suppositories can cause pain and discomfort for patients, may reach the end of the colon; consequently, the drug can undergo the first-pass effect. TS liquid suppository (TS-LS) was developed to enhance patient compliance and rectal mucosal safety in high-risk patients receiving highly NSAID therapy. This work was conducted to optimize and evaluate Poloxamer P407/P188-based thermoresponsive TS-LS by using mucoadhesive polymers such as methylcellulose (MC). TS-LS was prepared by cold method and characterized their in-vitro physicochemical properties as gelation temperature (GT), gel strength, bioadhesive properties and in-vitro release. The safety of the prepared suppository on rectum, stomach and liver was evaluated histologically. Pharmacokinetic a...